GLP-1: New Metrics, New Molecules, New Prices

Topics We Cover:

00:00 – New data from Harvard/Mass General may classify nearly 70% of adults as having obesity
03:00 – A new oral triple agonist shows record-setting absorption rates
07:00 – Fractal Health’s Revita procedure: weight maintenance after stopping GLP-1s
12:00 – Zepbound vial prices drop (full breakdown by dose)
16:00 – Dave’s personal experience switching off Mounjaro and intense hunger return
22:00 – Novo Nordisk’s EVOKE/EVOKE+ Alzheimer’s trial: what the data really means
29:00 – Why GLP-1 neurological research is just getting started
33:00 – Updates on access, partners, and major news coming soon for Medicare patients

If you’re on Wegovy, Mounjaro, Zepbound, Saxenda, Trulicity, or compounded versions, this episode gives you the insight and context you need to have more competent and confident conversations with your doctor.

Bullet Point Summary of the Podcast Episode

1. New Obesity Measurement Data (Harvard/Mass General Study)

Harvard and Mass General propose adding waist circumference to BMI to better diagnose obesity.

Traditional BMI misses key factors like muscle mass and body composition.

Using the updated measure, Americans classified as obese jumps from ~43% to almost 69%.

This means 7 out of 10 U.S. adults would now qualify as having the disease of obesity.

Dave notes this validates many people who “feel” metabolically unwell despite a “normal” BMI.

Reinforces his claim that “most people should be talking to their doctors about GLP-1s.”

1. New Oral Triple Agonist (Ascletis – ASC41/ASC? Molecule)

From Ascletis (A-S-C-L-E-T-I-S), developing an oral triple agonist targeting:

GLP-1

GIP

Glucagon

Similar in mechanism to retatrutide, expected around 2027.

Preclinical (animal) data show stunning results:

Oral bioavailability of 4.2%

9× higher than tirzepatide

30× higher than oral semaglutide

6× higher than oral retatrutide

57× greater drug exposure than oral retatrutide

Half-life ~56 hours

Stronger receptor activation than retatrutide in vitro

Suggests potential for the first powerful oral triple agonist—worth watching.

️ 3. Discussion of the Gray Market / TikTok Experience

Dave briefly recounts losing his TikTok account and landing in an algorithm filled with teenagers promoting gray-market “retatrutide.”

Expresses concern over unregulated peptide sales, especially to minors.

1. Fractal Health’s New Data – Weight Maintenance After Stopping GLP-1s

New results from the Reveal One study (Fractal Health).

Participants: lost 24% of body weight on GLP-1s → stopped injections → got one Revita procedure.

At 6 months post-GLP-1 discontinuation:

Weight changed only 1.5% (vs. ~10% regain in typical off-drug trials)

HbA1c barely shifted

Safety profile clean

Suggests possible long-term weight maintenance without injections through gut mucosal re-lining.

Dave describes his own recent attempt to switch drugs and significant hunger return.

1. Food Noise & Biologic Hunger

Dave discusses how stopping Mounjaro caused terrifying, primal hunger.

Describes the distinction between:

Food noise (brain-based thoughts)

Hunger signals (biological/animalistic)

Reinforces why many patients cannot maintain weight loss without support.

1. Zepbound (Tirzepatide) Cash-Pay Price Reductions

Eli Lilly drops cash-pay vial pricing:

2.5 mg: $349 → $299

5 mg: $499 → $399

7.5–15 mg: $499 → $449

Community feedback (informal poll):

Most say still too high to leave compounded versions.

Many would switch to branded if price hit $200–$300.

Dave notes the Most Fa

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